Tissue samples from a three-week old, Charolais mix, male intact calf were submitted to the Texas A&M Veterinary Medical Diagnostic Laboratory (TVMDL) for testing. According to the submitting veterinarian, the animal exhibited acute, non-specific neurological deficits that progressed rapidly. No information was provided regarding whether this animal died naturally or by euthanasia. Tests requested by the submitting veterinarian included histopathology, heavy metal panel analysis, Neospora caninum PCR, bovine viral diarrhea virus (BVDV) PCR, and bacterial culture.
On microscopy, and consistent with neurological deficits, the most prominent lesion was observed in the brain and consisted of multifocal neuronal necrosis, perivascular cuffs composed of lymphocytes, plasma cells, macrophages, neutrophils, glial nodules, and intranuclear inclusion bodies. Additional microscopic findings included a neutrophilic and histiocytic infiltrate accompanied with necrotic debris and fibrin in the small intestine and follicular lymphocytic hyperplasia in the mesenteric lymph node with draining neutrophils. Bacterial culture of the small intestine yielded Clostridium perfringens. Subsequently, beta-2 toxin and enterotoxin were detected in the isolate via rtPCR typing (Clostridium perfringens Type E). The hepatic levels of arsenic, cadmium, lead, and thallium were under the detection limit and zinc was normal. BVDV nucleic acid was not detected in the ear skin by rtPCR and Neospora caninum DNA was not detected in brain tissue PCR by rtPCR.
Given that the changes observed in the brain were highly suggestive of a viral infection, additional testing was performed in consultation with the submitter. A bovine herpesvirus rtPCR test that detects subtypes 1 and 5 was positive (Ct value 28.5) in the brain tissue of this animal. A gel-based PCR assay that differentiates the subtypes confirmed infection with bovine herpesvirus 5 (BHV-5).
BHV-5 is a viral pathogen that was originally classified as subtype BHV-1.3, to differentiate it from the BHV-1.1 and BHV-1.2 subtypes, which are known to primarily cause respiratory and genital disease, respectively. However, BHV-1 infection sometimes results in fatal encephalitis in cattle. Nonetheless, BHV-5 is one of the major causative agents of necrotizing meningoencephalitis in young cattle. Given that BHV-5 and BHV-1 are neurotropic and infection by either can result in similar microscopic lesions, it’s difficult to differentiate on histopathology alone. BHV-5 is endemic in South America but has been reported sporadically in other regions. In the United States, reports of infection with BHV-5 exist but its geographical distribution and prevalence is not known. Transmission of BHV-5 can occur from direct contact, aerosolization, or indirect contact through contaminated sources such as food, water, or semen. Proposed mechanisms for neuroinvasion in cattle include infection of the nasal mucosa and invasion of the central nervous system (CNS) through the olfactory and/or trigeminal nerves. Systemic infection, with viremia and subsequent neuroinvasion is another proposed mechanism for CNS infection. The frontal cortex and olfactory bulb have been described as prominent sites for viral replication. Infection by alpha-herpesviruses is characterized by cycles of acute infection, latency in the CNS, and reactivation, which is frequently accompanied by mild clinical signs. Lesions related to central nervous system infection are mainly due to neuronal degeneration/necrosis and inflammatory response. It is not clear whether commercially available vaccines for BHV-1 protect against BHV-5 infection.
TVMDL offers a rtPCR test that can detect BHV 1 and 5 and if requested, a follow-up gel-based PCR assay which differentiates the two.
For more information about TVMDL’s test offerings, visit tvmdl.tamu.edu or call 1.888.646.5623.